泰国非囊性纤维化患者脓肿分枝杆菌分离株的基因组分析：系统发育、亚种分布及抗菌药物耐药谱

Genomic analysis of Mycobacterium abscessus isolates from non-cystic fibrosis patients in Thailand: phylogeny, subspecies distribution, and antimicrobial resistance profiles.

作者信息

Prommi Ajala, Sawaswong Vorthon, Petsong Suthidee, Wongjarit Kanphai, Somsukpiroh Ubonwan, Payungporn Sunchai, Rotcheewaphan Suwatchareeporn

机构信息

Program in Bioinformatics and Computational Biology, Graduate School, Chulalongkorn University, Bangkok, Thailand; Center of Excellence in Systems Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.

出版信息

J Microbiol Immunol Infect. 2025 Aug 8. doi: 10.1016/j.jmii.2025.08.003.

DOI:10.1016/j.jmii.2025.08.003

PMID:40796429

Abstract

BACKGROUND

Mycobacterium abscessus (MABS) is a clinically significant nontuberculous mycobacterium, and its drug resistance poses substantial therapeutic challenges. Comprehensive genomic and phenotypic analyses are essential for elucidating the mechanisms underlying this resistance and enhancing understanding of its epidemiology.

METHODS

Whole-genome sequencing (WGS) using the Illumina platform was conducted on 61 clinical MABS isolates obtained from patients in Thailand. MABS subspecies classification was performed using FastANI, TYGS, and NTM-Profiler. Phenotypic drug susceptibility testing (pDST) was determined using a broth microdilution method. Resistance mutations were identified through NTM-Profiler and Snippy pipelines.

RESULTS

The analysis classified MABS isolates into three subspecies: subsp. abscessus (40/61, 65.57 %), subsp. massiliense (15/61, 24.59 %), and subsp. bolletii (6/61, 9.83 %). Phylogenetic analysis revealed genetic diversity among the majority of the MABS clinical isolates. These isolates clustered into distinct clades, separate from globally recognized clinical strains and dominant circulating clones. Inducible clarithromycin resistance was detected in 60.66 % of MABS isolates, associated with the T28 variant in erm(41). The Ile80Val mutation in erm(41) was significantly associated with inducible clarithromycin resistance (χ = 12.61, p < 0.001). Acquired clarithromycin resistance associated with rrl mutations (A2270C, A2270G, A2271C) and amikacin resistance linked to the rrs mutation A1375G were detected in 11.48 % and 4.92 % of isolates, respectively. The categorical agreement between WGS-based DST and pDST was 95.08 %, 88.33 %, and 96.43 % for inducible clarithromycin, clarithromycin, and amikacin, respectively.

CONCLUSION

This study provides valuable insights into the genomic diversity and antimicrobial resistance of MABS isolates in Thailand, emphasizing regional variations in dominant clones and resistance mechanisms.

摘要

背景

脓肿分枝杆菌（MABS）是一种具有临床意义的非结核分枝杆菌，其耐药性带来了巨大的治疗挑战。全面的基因组和表型分析对于阐明这种耐药性的潜在机制以及增进对其流行病学的理解至关重要。

方法

对从泰国患者中分离出的61株临床MABS菌株进行了使用Illumina平台的全基因组测序（WGS）。使用FastANI、TYGS和NTM-Profiler进行MABS亚种分类。采用肉汤微量稀释法进行表型药敏试验（pDST）。通过NTM-Profiler和Snippy流程鉴定耐药突变。

结果

分析将MABS菌株分为三个亚种：脓肿亚种（40/61，65.57%）、马西利亚亚种（15/61，24.59%）和博勒亚种（6/61，9.83%）。系统发育分析揭示了大多数MABS临床分离株之间的遗传多样性。这些分离株聚集成不同的进化枝，与全球公认的临床菌株和主要流行克隆不同。在60.66%的MABS分离株中检测到诱导型克拉霉素耐药，与erm(41)中的T28变体相关。erm(41)中的Ile80Val突变与诱导型克拉霉素耐药显著相关（χ = 12.61，p < 0.001）。在11.48%和4.92%的分离株中分别检测到与rrl突变（A2270C、A2270G、A2271C）相关的获得性克拉霉素耐药和与rrs突变A1375G相关的阿米卡星耐药。基于WGS的DST与pDST之间，诱导型克拉霉素、克拉霉素和阿米卡星的分类一致性分别为95.08%、88.33%和96.43%。